Helicobacter pylori chronically infects the gastric mucosa of billions of people worldwide, causes peptic ulcer disease in 10% or more of them, and is also implicated as an early critical risk factor for gastric cancer, one of the most frequently lethal malignancies in human populations (Suzuki et al., 2006, Carcinogenesis). However, the mechanisms by which H. pylori establishes and maintains colonization remains poorly understood. While these mechanisms remain poorly understood it is difficult to consider the development of useful vaccines against H. pylori. Moreover, the use of attenuated H. pylori as a biological delivery vehicle for peptides will remain elusive.
One of the first characterised factors essential for colonization by H. pylori was urease, an abundant enzyme that decreases the acidity of H. pylori's immediate environment by generating ammonia and carbonate from the urea we secrete as metabolic waste (Marcus & Scott, 2001, Helicobacter, 6(2), 93-99; Hu & Mobley, 1990, Infect. Immun., 58(4), 992-998). Although such local control of pH is considered essential, urease-negative H. pylori strains have been shown to be unable to colonise piglets whose acid secretion has been suppressed, suggesting an additional role for urease (Eaton & Krakowka, 1994, Infect. Immun., 62(4), 992-998).
In order to produce a more effective vaccine strain of H. pylori or a strain that could be used as a biological vehicle the inventors have studied the dodecamer surface contribution to urease acid stability and host interactions of H. pylori. 